Goodpasture Syndrome

Synonyms of Goodpasture Syndrome

Pneumorenal Syndrome

General Discussion

Goodpasture syndrome is a rare autoimmune disorder characterized by inflammation of the filtering structures (glomeruli) of the kidneys (glomerulonephritis) and excessive bleeding into the lungs (pulmonary hemorrhaging). Autoimmune syndromes occur when the body's natural defenses (antibodies) against invading or "foreign" organisms begin to attack the body's own tissue, often for unknown reasons. Symptoms of Goodpasture syndrome include recurrent episodes of coughing up of blood (hemoptysis), difficulty breathing (dyspnea), fatigue, chest pain, and/or abnormally low levels of circulating red blood cells (anemia). In many cases, Goodpasture syndrome may result in an inability of the kidneys to process waste products from the blood and excrete them in the urine (acute renal failure). In some cases of Goodpasture syndrome, affected individuals have had an upper respiratory tract infection before the development of the disorder. The exact cause of Goodpasture syndrome is not known.

Signs & Symptoms

The major symptoms of Goodpasture syndrome are excessive bleeding into the lungs (pulmonary hemorrhaging) and inflammation of the filtering structures (glomeruli) or the kidneys (glomerulonephritis). In some cases, an upper respiratory tract infection may precede the development of the disorder. General symptoms associated with Goodpasture syndrome may include fever, nausea, and fatigue.

Pulmonary hemorrhaging may lead to episodes where affected individuals cough up blood (hemoptysis). The severity of this finding may range from a few flecks to excessive amounts of blood. Affected individuals may also exhibit difficult breathing (dyspnea), fatigue, chest pain, a dry rasping sound from the throat (rhoncus), and/or frequent coughing. In rare cases, affected individuals may exhibit abnormal accumulation of fluid (edema) in the tissue of the lungs. Pulmonary abnormalities are usually noted before or simultaneous to kidney (renal) abnormalities in approximately 70 percent of the cases.

Inflammation of the filtering structures (glomeruli) of the kidneys (glomerulonephritis) may lead to an inability of the kidneys to process waste products from the blood and excrete them in the urine (acute renal failure). Renal failure usually leads to a decrease in the amount of urine the body produces. Additional symptoms associated with renal failure may include abnormally pale skin (pallor), drowsiness, nausea, and/or vomiting. Severe complications of renal failure include bleeding into the stomach and/or a decrease in the amount of circulating red blood cells (anemia).

In rare cases, affected individuals may exhibit high blood pressure (hypertension) and/or pain and swelling of the joints (arthritis). In some cases, symptoms of Goodpasture syndrome may recur after treatment.

Causes

Goodpasture syndrome develops due to unknown causes. Environmental factors such as hydrocarbon chemical exposure, cigarette smoke, or infections such as influenza may play a role in the development of the disorder. It is not known why simple infections can progress to Goodpasture syndrome in some people. When infection occurs, the body’s natural defenses (antibodies) fight the invading organisms (e.g., viruses or bacteria). In autoimmune disorders, antibodies attack healthy tissue for no apparent reason. Pulmonary hemorrhage has been frequently associated with smoking in individuals with Goodpasture syndrome.

In Goodpasture syndrome, certain antibodies (anti-glomerular basement membrane [anti-GBM] antibodies) may be produced and circulate throughout the blood. These antibodies may damage the delicate membranes that line the lungs and kidneys or the tiny blood vessels (capillaries) within the lungs and kidneys.

In some cases, individuals with Goodpasture syndrome may have an association with human leukocyte antigens (HLAs). HLAs are proteins that play an important role in the body’s immune system; they influence the outcome of transplantation and appear to affect an individual’s predisposition to certain diseases. However, the implications of such findings are not fully understood.

Goodpasture syndrome has been reported in more than one family member (e.g., siblings) in a few cases, supporting the possibility of genetic susceptibility as a factor in some cases. A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances, such as due to particular environmental factors (multifactorial inheritance).

Affected Populations

Goodpasture syndrome is a rare autoimmune disorder that appears to affect males more frequently than females. Age of onset is usually between 20 and 30, but individuals at any age may be affected.

Goodpasture syndrome was first identified in 1919. Since that time approximately 600 cases have been noted in the medical literature.

In the US the Anti-GBM disease is an uncommon disorder; approximately 1-2% of all cases of rapidly progressive glomerulonephritis are secondary to this disorder.

Related Disorders

Symptoms of the following disorders can be similar to those of Goodpasture syndrome. Comparisons may be useful for a differential diagnosis:

Wegener’s granulomatosis is an uncommon disorder characterized by inflammation of blood vessels (vasculitis) that results in damage to various organ systems of the body, most often the respiratory tract and kidneys. Symptoms may include ulcerations of the mucous membranes in the nose with secondary bacterial infection, a persistent runny nose, sinus pain, and chronic middle ear infection (otitis media) potentially resulting in hearing loss. In some cases, kidney abnormalities may progress to kidney failure, a serious complication. If the lungs are affected, a cough, expectoration of blood (hemoptysis), and inflammation of the thin membrane lining the outside of the lungs and the inside of the lung may be present. The exact cause of Wegener’s granulomatosis is not known. (For more information on this disorder, choose “Wegener’s” as your search term in the Rare Disease Database.)

Idiopathic pulmonary hemosiderosis is a lung disorder similar to Goodpasture syndrome. Affected individuals may also have secondary iron-deficiency anemia. It seems to occur mostly in young children, and does not have the antibody reaction found in Goodpasture syndrome. The exact cause of this disorder is unknown (idiopathic).

Bacterial endocarditis is a lung and kidney disorder that has some clinical similarities to Goodpasture syndrome, but also involves the heart. Bacterial endocarditis is caused by bacterial infection. Affected individuals may develop heart murmurs as well as artery blockage (embolisms). Skin lesions, spleen enlargement, and intermittent high fever are other symptoms associated with this disorder.

Diagnosis

A diagnosis of Goodpasture syndrome may be suspected based upon the identification of characteristic physical findings (e.g., pulmonary hemorrhaging and glomerulonephritis). The diagnosis may be confirmed by the identification of the presence of anti-glomerular basement membranes antibodies in the body. In some cases, affected individuals may exhibit blood (hematuria) and/or protein (proteinuria) in the urine.

Standard Therapies

Treatment

Mild forms of Goodpasture syndrome may be treated with the use of drugs that suppress or hinder the effectiveness of the body's immune system (immunosuppressive drugs). Corticosteroids such as prednisone may be administered to control bleeding in the lungs (pulmonary hemorrhaging).

Many affected individuals may be treated with plasmapheresis. This procedure is a method for removing unwanted substances (toxins, damaging antibodies, and metabolic substances) from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is transfused into the patient. This therapy is still under investigation to analyze side effects and effectiveness. Plasmapheresis is often administered in conjunction with corticosteroid treatment.

In severe and repeated cases of Goodpasture syndrome affected individuals may be treated with a procedure where waste products are removed from the blood (dialysis). In the most severe cases, a kidney transplant may be needed.

Investigational Therapies

Changes from nonspecific to more selective methods of plasmapheresis are under investigation in the treatment of Goodpasture syndrome as well as many other autoimmune disorders. These methods may include cascade filtration, cryofiltration, immunoabsorption, enzymatic degradation, and continuous electrophoresis. These procedures appear to be significant advances in clinical and experimental immunology therapeutic research. In immunoabsorption, only immunoglobulins (antibodies) are removed from an affected individual’s blood stream.

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